This study has two components: the first involves the long-term followup of patients enrolled in the National Institutes of Health (NIH) prospective studies of transfusion-associated hepatitis and the second represents a multicenter retrospective-prospective study that incorporates the subset of NIH patients who were transfused between 1969 and 1983. The goal of both aspects of the study is to determine the persistence of hepatitis C virus (HCV) infection and the chronic consequences of that infection. It is apparent from the NIH cohort that 85 percent of patients infected with HCV become chronic carriers of the virus as assessed by polymerase chain reaction and that 15 percent resolved their infection within 1 year of onset. Most patients with persistent viremia have some evidence of chronic hepatitis based on serial alanine aminotransferase determinations and liver biopsy. Of those biopsied, approximately 20 percent have histologic evidence of cirrhosis, although only half of those patients have had clinical evidence of cirrhosis. The rate of liver-related mortality within the first two decades of followup has been 4 percent. In the multicenter study, 568 persons with transfusion-associated non-A, non-B hepatitis (predominantly hepatitis C) were compared with 984 carefully matched controls who were transfused but did not develop hepatitis. After an average followup of 18 years, all-cause mortality was 51 percent in the hepatitis group and 52 percent in the controls (not significant). There was an increase in liver- related mortality in the hepatitis group, but it was slight (3.3% versus 1.4%, p=0.033). Seventy-one percent of the deaths caused by liver disease occurred in patients with associated chronic alcoholism. Long-term clinical followup and further analysis of virology, serology, and histology continue.